The aim of this investigation was to explore the nature and the severity of circadian abnormalities and attentional deficit in type 1 narcolepsy. In three studies, narcolepsy patients were compared with patients suffering from other central disorders of hypersomnolence and healthy controls on attentional functions and circadian rhythms. Study 1 evaluated the sensibility of actigraphic monitoring in distinguishing the features of daytime and nighttime sleep between adult patients with type 1 Narcolepsy, Idiopathic Hypersomnia and healthy controls. Actigraphy provides a reliable assessment of sleep quality and daytime napping behavior able to distinguish central disorders of hypersomnolence and identify Narcolepsy Type 1 patients. Study 2 describes the features of circadian activity rhythm of narcolepsy type 1 children with recent disease onset. Type 1 narcolepsy children and healthy children were monitored for seven days during the school week, circadian activity rhythms were analyzed through functional linear modeling. Children with type 1 narcolepsy present an altered rest-activity rhythm characterized by enhanced motor activity throughout the night and blunted activity in the first afternoon. The observation of a discrete circadian profile provides new insight on the nature of diurnal variations and suggested that the quantitative assessment of motor activity is a promising behavioral biomarker of Type 1 narcolepsy. The aim of Study 3 was to explore the nature and the severity of attentional Deficits of Narcoleptic patients. This study examined whether narcoleptic patients would exhibit impairments in alerting, orienting, and executive control of attention relative to healthy controls. Narcoleptic patients present a deficit in alerting network, while orienting and executive control networks resulted preserved. Moreover the alerting network efficiency significantly correlate with levels of subjective sleepiness. Results indicates that in narcolepsy the unstable tonic component of alerting process make necessary monitoring and compensation strategies.

La vicenda personale di Michele Sindona è utile per ricostruire l'economia italiana degli anni sessanta e settanta. Divenuto uno dei massimi esperti in Italia nell'evasione del fisco e nell'esportazione di capitali all'estero, il banchiere si insinua nel capitale di Banca unione e Banca privata finanziaria acquisendo le partecipazioni della famiglia Feltrinelli. Il tentativo di scalare la Bastogi viene bloccato dal governatore di Bankitalia. Il banchiere cerca l'apoggio negli States della comunità italo americana e della P2 di Licio Gelli. La sua competenza in materia finanziaria e i suoi legami lo rendono il punto di contatto ideale tra ideali dei circoli repubblicani atlantici e la sponda anticomunista facente capo alla Dc e alla P2 in Italia. / The aim of the present thesis is to describe the Italian economic context in which Michele Sindona worked. He soon became the most famous italian expertice in financial advisory and tax; at that time he also come into contact with Moizzi which gave him its personal shares in” financial Private Bank” and, thanks to the good relation with Cesare Merzagora, he catched the stock of the Feltrinelli family so granting himself the access to the “Union Bank's capital” ; Sindona seems to transfer his activities to the States. After the OPA defeat in '72 the group's activities begin to operate outside of any legal ; Infact By Fasco Ag, a Lichtenstein brokerage , Sindona export capital on deposit at foreign sited branch banks ;this way of doing allows him to act outside of any legal constraint, virtually masking financial activities. The creation of Moneyrex, the first Italian agency broker, made the Sindona group began to expose too heavily in the foreign exchange market. The economic crisis of '74 leads to the collapse of the Franklin Bank and other institutions of the group.
Clashing with the Industrial Italian financial establishment Sindona preclude himself at the end any attempt to reform the Italian financial system ,so strictly connected to the Statal Industry and to the Italian political party system. The banker was involved in the defeat of the referendum on divorce in 1974 that he had generously funded. Not any more able to count on the Dc his fate is always more tied up to P2; the banker is so used by that organization to finance its economic activities. Sindona is finally crushed by the Italian economy and political system tied to opposing blocs of the Cold War.

Questa ricerca ha per oggetto lo studio dell’influenza del Giappone sulla moda italiana, dalla metà del XVI alla fine del XX secolo. Le prime notizie sugli abiti giapponesi giunsero in Italia intorno al 1550, dopo che il Giappone era stato ‘scoperto’ nel 1543 da alcuni mercanti portoghesi naufragati sulle sue coste. Tuttavia i primi timidi influssi giapponesi nella moda italiana si manifestarono solo dopo la seconda metà del XVII secolo, quando i nobiluomini italiani cominciarono a indossare kimono giapponesi come vesti da camera. Inoltre in alcuni tessuti di produzione italiana furono introdotti schemi decorativi desunti dalle contemporanee stoffe nipponiche. Ma fu solo alla fine dell’Ottocento che scoppiò in Europa e in Italia una diffusa passione per il Giappone e per la sua cultura, che è stata definita giapponismo. Dal momento che la moda è lo specchio dei tempi, anche la moda italiana, tra gli anni Ottanta dell’Ottocento e gli anni Venti del Novecento, venne percorsa da insistiti riferimenti all’abbigliamento giapponese, in particolar modo al kimono. Dopo il giapponismo tardo ottocentesco, il secondo periodo in cui sono riscontrabili evidenti influssi giapponesi sulla moda italiana si colloca tra gli anni Settanta e gli anni Novanta del Novecento. Durante questa fase di neo-giapponismo, alcuni stilisti italiani come Mila Schön e Ken Scott hanno continuato a trarre ispirazione dai costumi giapponesi tradizionali. Altri, invece, come Romeo Gigli ed Ennio Capasa, sono stati influenzati dai fashion designers giapponesi contemporanei Kenzo Takada, Issey Miyake, Yohji Yamamoto e Rei Kawakubo, che proponevano abiti oversize, spesso informi e asimmetrici. / The aim of this paper is to investigate the influence of Japan on Italian fashion from the half of the XVIth century to the end of the XXth century. The first information on Japanese clothes reached Italy around 1550, after Japan was ‘discovered’ by some Portuguese sailors who arrived on Japanese coasts after a shipwreck in 1543. However, the first mild influences of Japan on Italian fashion can be seen only after the second half of the XVIIth century when Italian noblemen started wearing kimonos as night-gowns. In addition, at that time, Japanese-style patterns derived from Japanese fabrics were introduced in some Italian fabrics. But it was just at the end of the XIXth century that a sort of Japanese culture mania called Japonisme spread out in Europe and in Italy. Since fashion is a reliable mirror of its times, also Italian fashion between 1880 and 1920 experienced more than once the influence of Japanese clothing, especially of the kimono. After late XIXth century Japonisme, the second time when Italian fashion was profoundly influenced by Japan was between the Seventies and the Nineties of the XXth century. During that phase of neo-Japonisme, some Italian fashion designers such as Mila Schön and Ken Scott repeatedly drew inspiration from old Japanese clothes. Others, such as Romeo Gigli and Ennio Capasa were influenced by contemporary Japanese fashion designers such as Kenzo Takada, Issey Miyake, Yohji Yamamoto and Rei Kawakubo who designed over-size clothes, often shapeless and asymmetrical.

At the core of this doctoral submission is a portfolio of three of my recent choreographic works(all created between 2011-2014), complemented by a text, which attempts to formulate a theoretical approach for explicating the works, through the lens of Theodor Adorno’s theory of the inherent negativity of modernist artworks. Such an approach places Adorno’s ideas at the very centre of the analytical view presented here, albeit via the semiotic (re)articulation of these same ideas in recent work by Christoph Menke. This, in turn, draws on earlier work done within aesthetic semiotics by Viktor Shklovsky, through which it is hoped that insight, clarification, and historical contextualisation will be forthcoming, whilst also casting an eye on the contemporary situation within arts making. The thesis is therefore a theoretical analysis of aesthetically negative philosophical thought within choreographic practice, but simultaneously it is an attempt to point to new knowledge; namely an enhancement of Menke's semiotic reading of Adorno, extended from the field of literature from which it originates, and brought into the field of dance, movement, and choreography. In addition to this, a vital second aspect of my approach will be a consideration of the extra - semiotic aspects of dance, read through a phenomenological understanding of kinaesthesia, and how our understanding of movement and choreography is rooted in basic aspects of our perceptive capabilities. Prior to the introduction, the beginning of this thesis, there is a presentation of factual information regarding the production aspects of the performances in a brief Foreword. The structure of the thesis is then as follows. The Introduction offers a short historic overview of Adorno’s theory of ‘aesthetic negativity’, and this is followed by three Chapters, titled: (1) Object and Subject, (2) Recombination, and (3) Projection. These three notions are not only essential to my work as methodological tools, but they also provide important references, connections and bilateral correspondences to similar concepts within Adorno’s aesthetic theory, thereby clarifying the relationship between theory and practice in my work. Chapter Four aims to re-inspect the works comprising The Urban Series in a similar fashion, while also placing their specific context within external, everyday and urban environments under critical examination.

Le but de cette thèse est de développer une stratégie pro-apoptotique à partir des paramètres pouvant moduler l’apoptose photoinduite par le Foscan® dans des modèles précliniques d’adénocarcinome humain. La PDT avec le Foscan® a été appliquée in vitro sur lignées cellulaires où une apoptose modérée a été obtenue via l’implication indirecte de la voie mitochondriale. La modulation de l’apoptose photoinduite par l’oxygénation a été démontrée sur sphéroïde, modèle de micro-tumeur non vascularisée. Une irradiance faible, garantissant le maintien de l’oxygénation du sphéroïde, favorise l’activation de la caspase-3 photoinduite par le Foscan®. Le deuxième paramètre favorisant l’apoptose photoinduite est l’accroissement du temps d’incubation du photosensibilisateur avec les cellules MCF-7, ce qui modifie sa localisation subcellulaire. Après 3h d’incubation, le Foscan® est essentiellement localisé dans le réticulum endoplasmique (RE) et l’appareil de Golgi. Après irradiation, le stress oxydant du RE évalué par l’induction de la protéine chaperone GRP78 suivie de la réponse apoptotique mitochondriale et de l’activation des caspases a été observée. Après 24h d’incubation, la localisation dans le RE est renforcée ainsi que l’expression photoinduite de GRP78 corrélée avec une augmentation de l’activation caspase-7 indépendamment de la réponse mitochondriale. Après PDT in vivo, l’estimation par immunohistochimie sur coupe tissulaire de l’activation des caspases -7 et -3 montre une activation prédominante de la caspase-3 ce qui suggère une apoptose majoritairement dépendante de cette dernière dans les tumeurs d’adénocarcinome colique HT29 traitées par Foscan®-PDT. / In order to develop a proapoptotic strategy in Foscan®-mediated photodynamic therapy (PDT) an evaluation of the parameters that govern the modulation of photoinduced apoptosis was performed on preclinical model from human adenocarcinoma. Moderate apoptosis was measured in Foscan® photosensitised tumour cells in vitro. The mitochondrial pathway was assumed to be indirectly induced by Foscan®-PDT. Spheroids were used to investigate the influence of oxygen consumption, through the modulation of fluence rate, on the induction of apoptosis. By using a low fluence rate, an oxygen conservative regimen, we demonstrated an increase in the activation of caspase-3 induced by Foscan®-PDT. The modulation of photoinduced apoptosis by extending the incubation time of Foscan® with MCF-7 cells was further investigated. After 3h incubation, the photosensitizer was mainly localised in the endoplasmic reticulum (ER) and Golgi apparatus. Following irradiation, ER oxidative stress through the induction of the chaperon protein GRP78 was observed. Subsequent apoptotic mitochondria response and caspase activation were induced. After 24h incubation with Foscan®, the ER localisation of the photosensitizer was intensified. As results, an increase in GRP78 expression correlated with an increase in caspase-7 activation independently of the mitochondria response was obtained. After in vivo PDT, immunohistochemistry was applied on tissue sections to evaluate the activation of caspases -3 and -7. Caspase-3 activation was found predominant suggesting a caspase-3 mediated apoptotic pathway in HT29 tumours subjected to Foscan®-PDT.

L'algorithme FastICA est l'un des algorithmes les plus populaires dans le domaine de l'analyse en composantes indépendantes (ICA). Il existe deux versions de FastICA: Celle qui correspond au cas où l'échantillon est de taille infinie, et celle qui traite de la situation concrète, où seul un échantillon de taille finie est disponible. Dans cette thèse, nous avons fait une étude détaillée des vitesses de convergence de l'algorithme FastICA dans le cas où la taille de l'échantillon est finie ou infinie, et nous avons établi cinq critères pour le choix des fonctions de non-linéarité. Dans les trois premiers chapitres, nous avons introduit le problème de l'ICA et revisité les résultats existants. Dans le Chapitre 4, nous avons étudié la convergence du FastICA empirique et le lien entre la limite de FastICA empirique et les points critiques de la fonction de contraste empirique. Dans le Chapitre 5, nous avons utilisé la technique du M-estimateur pour obtenir la normalité asymptotique et la matrice de covariance asymptotique de l'estimateur FastICA. Ceci nous a permis aussi de déduire quatre critères pour choisir les fonctions de non-linéarité. Un cinquième critère de choix de non-linéarité a été étudié dans le chapitre 6. Ce critère est basé sur une étude fine de la vitesse de convergence de FastICA empirique. Nous avons illustré chaque chapitre par des résultats numériques qui valident nos résultats théoriques. / The FastICA algorithm is one of the most popular algorithms in the domain of Independent Component Analysis (ICA). There exist two versions of FastICA: the one that corresponds to the ideal case that the sample size is infinite, and the one that deal with the practical situation, where a sample of finite size is available. In this thesis, we made a detailed study of the rate of convergence of the FastICA algorithm of both versions, and we established five criteria for the choice of the non-linearity function. In the first three chapters, we introduced the problem of ICA and revisited the classical results. In Chapitre 4, we studied the convergence of empirical FastICA and the link between the limit of empirical FastICA and the critical points of the empirical contrast function. In Chapter 5, we used the technique of M-estimator to obtain the asymptotic normality and the asymptotic covariance matrix of the FastICA estimator. This allowed us to derive four criteria to choose the non-linearity function. A fifth criterion for the choice of the non-linearity function was studied in Chapter 6. This criterion is based on the rate of convergence of the empirical FastICA algorithm. At the end of each chapter, we provided numerical simulations that validate our theoretical results.

Die von CD5-positiven B-Zellen produzierten natürlichen Antikörper sind humorale Bestandteile des angeborenen Immunsystems. Sie kommen im Körper bereits vor, ohne dass ein Antigen-Kontakt stattgefunden hat und dienen dazu, den Organismus schnell und effektiv vor eindringenden Pathogenen zu schützen, möglichst noch bevor die erworbene Immunabwehr aktiviert werden muss. Zudem werden körpereigene Moleküle erkannt, die normalerweise geschützt intrazellulär vorliegen und erst bei Zellnekrose freigesetzt und so dem Immunsystem zugänglich gemacht werden. Außerdem konnten mit Hilfe der humanen Hybridoma Technologie aus Krebspatienten und gesunden Probanden natürliche Antikörper isoliert werden, die transformierte Zellen erkennen und beseitigen. Die natürlichen Antikörper sind keimbahncodiert und erhöhen im Gegensatz zu Antikörpern der erworbenen Immunabwehr nicht ihre Variabilität durch Mutationsereignisse und Reifung. In früheren Studien wurde beobachtet, dass natürliche Antikörper nicht spezifisch ein Antigen binden, sondern dass bestimmte häufig vorkommende und in der Evolution konservierte Antigen-Muster erkannt werden. Daraus folgerte man, dass natürliche Antikörper ihre Antigene „unspezifisch“ binden, so dass sich eine Vielzahl von Kreuzreaktionen mit verschiedenen Antigenen ergibt. Derartige Kreuzreaktionen der natürlichen Antikörper wurden bereits 1986 beschrieben. Ziel der vorliegenden Arbeit war zu zeigen, dass es innerhalb der natürlichen Antikörper verschiedene Pools mit unterschiedlichen Aufgaben gibt und dass natürliche Antikörper nicht wahllos beliebige Antigene binden, sondern dass sich ihr Reaktionsmuster aus ihrer Aufgabe innerhalb des menschlichen Immunsystems ergibt. Es wurden anhand des ELISA-Verfahrens Kreuzreaktionen der natürlichen Antikörper mit humaner DNA, körpereigenen Zytoskelettproteinen (Actin, Myosin, Keratin, Desmin, Vimentin) und Molekülen untersucht, die die innate Immunabwehr über Toll-like-Rezeptoren aktivieren können (LPS, LTS, PGN, Flagellin, HSP 70, bakterielle DNA, H.pylori-CagA und -VacA). Es konnte gezeigt werden, dass den 17 untersuchten Antikörpern CM-1, CM-2, LM-1, M6, NORM-1, NORM-2, NORM-3, NORM-4, PAM-1, PM-1, PM-2, SAM-1, SAM-3, SAM-4, SAM-5, SAM-6, SC-1 hauptsächlich die Aufgabe zukommt, transformierte Zellen zu beseitigen. Ihre Reaktionsweise ist also nicht „unspezifisch“, sondern „oligospezifisch“ innerhalb ihres Aufgabenbereichs. Zudem fiel in früheren Studien eine deutliche Korrelation zwischen der Anzahl durchgemachter Mutationen und dem Reaktionsmuster der Antikörper mit Tumorzellen auf: keimbahncodierte Antikörper ohne Mutationen reagierten immer mit einem breiten Spektrum verschiedener Tumore oder sogar Vorläuferläsionen, wohingegen das Spektrum der Reaktionen mit steigender Zahl von Mutationen abnahm. Bei den in dieser Arbeit untersuchten Antigen-Antikörper-Reaktionen konnte kein eindeutiger Zusammenhang zwischen der Reaktionsweise und dem genetischen Ursprung oder der Anzahl durchgemachter Mutationen hergestellt werden. / Natural antibodies are produced by CD5+ B-cells and represent humoral components of the innate immunity. They exist without the need for any contact to antigens and serve to defend the organism from external invaders like bacteria and viruses in a fast and effective way and preferably before the adapted immunity has to be activated. Moreover, normally intracellular located self-molecules are recognized when they are released during the process of cell necrosis. Natural antibodies could even be isolated from tumor-patients and healthy subjects by human hybridoma technology. These antibodies recognize and remove transformed cells. Natural antibodies are germ-line coded and do not increase their variability by mutational events and maturation in contrast to antibodies of the adapted immunity. As shown in former studies natural antibodies don’t bind a specific antigen but recognize frequently occurring patterns which have been conserved in the evolution. Due to this fact natural antibodies are called “unspecific” with a wide range of cross-reactions with various antigens. Such cross-reactions of natural antibodies have already been described in 1986. The aim of this work was to show that different pools of natural antibodies are existing. They have got varying tasks and they do not bind any antigens randomly. Their reactivity pattern is a consequence of their function in the human immune system. Cross-reactions with human DNA, body’s own proteins (actin, myosin, keratin, vimentin, desmin) and molecules which are able to activate the immune defence by Toll-like receptors (lipopolysaccharides, lipoteichoic acid, peptidoglycan, flagellin, heat-shock protein 70, bacterial DNA, CagA and VacA of H.pylori) have been tested by ELISA. It could be shown that the 17 tested antibodies CM-1, CM-2, LM-1, M6, NORM-1, NORM-2, NORM-3, NORM-4, PAM-1, PM-1, PM-2, SAM-1, SAM-3, SAM-4, SAM-5, SAM-6, SC-1 mainly serve to remove transformed cells. So their way of reacting is not “unspecific” but “oligo-specific” within their function. Furthermore, when natural antibodies were incubated with tumor tissues a striking correlation between the number of mutations and the reactivity pattern was apparent: germ-line coded antibodies without mutations always reacted with a broad spectrum of different tumors and even prelesions whereas the spectrum of reactivity decreased with an increasing amount of mutational events. The examined reactions between the tested antigens and antibodies did not lead to a clear correlation between the reactivity pattern and the genetic origin or the amount of mutations.

Die Entstehung maligner Zellen durch irreversible genetische Veränderungen ist ein allgegenwärtiger Prozess im menschlichen Organismus. Allein die spontane Mutationsrate genügt um in einem Organismus permanent transformierte Zellen entstehen zu lassen, welche den Körper in kürzester Zeit überschwemmen würden. Auch wenn bestimmte genetische Schäden frühzeitig durch Reparaturmechanismen beseitigt werden und sich nicht jede transformierte Zelle in einem Tumor manifestiert, so ist die eigentliche Frage nicht, warum Krebs entsteht, sondern warum er bei der hohen Mutationsrate so selten auftritt. Verantwortlich für die frühe Erkennung und Beseitigung transformierter Zellen ist das körpereigene Immunsystem, das in der Lage ist die meisten aberranten Zellen zu entfernen, sodass der manifeste Tumor die Ausnahme und nicht die Regel ist. Der menschliche Organismus verfügt über ein angeborenes und ein erworbenes Immunsystem. Bis heute ist nicht eindeutig geklärt, ob maligne Zellen mit ihren veränderten Oberflächenstrukturen erst eine Immunantwort induzieren müssen oder ob, wie bei der Abwehr infektiöser Partikel, die angeborene Immunität für die Beseitigung von Tumorzellen verantwortlich ist. Die in dieser Arbeit verwendete humane Hybridoma Technologie (Immortalisierung menschlicher Lymphozyten und Isolierung monoklonaler Antikörper) bietet die einzigartige Möglichkeit, sowohl aus an Krebs erkrankten Patienten als auch aus gesunden Probanden tumorspezifische Antikörper zu isolieren und durch deren genauere Charakterisierung Einblicke in die humorale Immunität gegen maligne Zellen zu erhalten. In der vorliegenden Arbeit werden fünf humane monoklonale Antikörper beschrieben, die aus verschiedenen Tumorpatienten gewonnen wurden, sowie zwei Antikörper, die aus gesunden Probanden isoliert werden konnten. In allen Fällen erwiesen sich die Antikörper als tumorspezifisch, d.h. sie reagieren nicht mit gesundem Gewebe und sind demnach keine Autoantikörper. Es handelt sich weiterhin in allen Fällen um Antikörper des IgM-Isotyps; es konnten keinen Antikörper anderer Ig-Klassen isoliert werden. Genetische Analysen ergaben, dass alle isolierten Antikörper gering oder gar nicht mutiert waren, was bedeutet, dass sie nicht durch Stimulation affinitätsgereift sind. Zudem konnte demonstriert werden, dass alle Antikörper Apoptose von Tumorzellen induzieren und dass sie an eine Zuckerkette ihrer Antigene binden oder solche Carbohydrate zumindest entscheidend in die Bindung involviert sind. Die Eigenschaften der in dieser Arbeit beschriebenen Antikörper wurden mit anderen bereits etablierten IgM-Antikörpern verglichen. Hierbei stellte sich heraus, dass alle Antikörper, welche sich als tumorspezifisch erwiesen, ähnliche Eigenschaften zeigen. Interessant ist zudem die Beobachtung, dass die Keuzreaktion der Antikörper, also ihre Reaktion mit anderen Tumorgeweben, reziprok mit dem Mutations-grad korreliert ist. Je mehr Mutationen ein Antikörper aufweist, desto eingeschränkter und spezifischer sind demnach seine Reaktionen mit anderen Tumoren. Dies deutet darauf hin, dass auch innerhalb der Keimbahn-kodierten Antikörper durch vereinzelte Mutationen eine höhere Variabilität erzeugt werden kann. Ähnlich wie bei der Affinitätsreifung der erworbenen Immunität scheint sich auch hier die Spezifität mit der Anzahl der Mutationen zu erhöhen. Zusammenfassend weisen die erhaltenen Ergebnisse darauf hin, dass zumindest die humorale Immunität gegen maligne Zellen das Resultat der angeborenen Immunität ist und nicht von Tumorzellen induziert wird. Dies bedeutet zudem, dass Moleküle wie natürliche Antikörper in der Immunität eine viel größere Rolle spielen als bisher angenommen. Ähnliche Ergebnisse wurden bereits bei der Untersuchung der Immunität gegen bakterielle Antigene erzielt, sodass hier vermutet werden kann, dass die gleichen Mechanismen zugrunde liegen wie bei der Abwehr transformierter Zellen. Darüber hinaus wird die Frage beantwortet, warum ein manifester Tumor eine Ausnahme bleibt. Die angeborene, primäre Immunität verfügt über ein existierendes Repertoire an Rezeptoren, welche eine ausreichende Variabilität aufweisen, und muss daher nicht erst über ein komplexes System von Erkennung und Stimulation, wie die adaptierte Immunität, induziert werden. Dieser logistische Vorsprung der natürlichen Immunität garantiert eine permanente Überwachung und eine schnelle Reaktion gegenüber veränderten Zellen und fremden Partikeln. / The formation of malignant cells through irreversible genetic alterations is a chronic process in a human organism. The spontaneous mutation rate is high enough to let transformed cells arise permanently in an organism and to flood the body with these cells in a short period of time. Although specific genetic damages were eliminated very early by repair mechanisms and not every transformed cell became a manifest tumour, the major question to be answered is not why cancer arises but why it occurs so infrequently despite of the high mutation rate. The immune system is responsible for the early detection and elimination of transformed cells. It is able to remove most of the transformed cells so that tumour formation is the exception but not the rule. The immune system of the human organism consists of an innate and an acquired system. Until the present time it is not explained definitely, whether malignant cells with their altered surface structure have to induce an immune answer or if the innate immunity is responsible for the elimination of tumour cells like for infectious particles. In this dissertation the human hybridoma technology (immortalisation of human lymphocytes and isolation of human monoclonal antibodies) was used to investigate this question. This technique offers the unique possibility to isolate tumour-specific antibodies from cancer patients as well as from healthy persons and to attain additionally insights into the humoral immunity against malignant cells. Five human monoclonal antibodies were described which were isolated from different cancer patients and in addition two antibodies obtained from healthy donors. In all of the cases the antibodies prove to be tumour-specific which means they do not react with healthy tissues and are according to this no auto-antibodies. All of them are IgM antibodies, no tumour-specific IgA or IgG antibody was detectable. Genetic analysis show that all isolated antibodies were only slightly mutated or not mutated at all, which means that they were not affinity-maturated due to antigen stimulation. Furthermore it was possible to demonstrate that all isolated tumour-specific IgM antibodies induce apoptosis in tumour cells. Another result indicates that carbohydrates are involved in the binding of the antibodies to their corresponding antigen. The characteristics of the antibodies were compared with other IgM antibodies which were already established in our lab. Here all antibodies which prove to be tumour-specific show similar characteristics. Interestingly the amount of cross reactivity with other tumour tissues correlates reciprocally with the degree of mutations. The more mutations an antibody displays the more reduced are the reactions with other tumour tissues. This indicates that, similar to the affinity-maturation of adapted immunity, an increase of specificity and most likely also variability of germ-line coded antibodies can be generated by few mutations. Our observations indicate that the humoral immunity against malignant cells is the result of the innate immunity. This means moreover that molecules like natural antibodies play a much more important role in immunity than assumed so far. Similar results were obtained already with analysis of immunity against bacterial antigens. This leads to the assumption that here the same mechanisms are involved like in the defence against transformed cells. Moreover the question could be answered why a manifest tumour remains an exception. The innate, primary immunity has an existing repertoire of receptors which are variable enough so that a complex system of recognition and stimulation like in the acquired immunity does not have to be induced. This logistic advantage of the natural immunity guarantees a permanent control and a fast reaction towards altered cells and foreign particles.

A endometriose é uma doença caracterizada pela presença de endométrio fora do útero. O estudo objetivou detectar Mollicutes (M. genitalium, M. hominis, U. urealyticum e U. parvum), HPV e N. gonorrhoeae em amostras de swab endocervical, fluido peritoneal e tecido de biópsia de mulheres com (grupo caso) e sem endometriose (grupo controle) e avaliar os achados com a endometriose. No swab endocervical, prevalências de M. hominis (Mh), M. genitalium (Mg), U. urealyticum (Uu) e HPV foram maiores no grupo caso (43,7%, 14,1%, 8,5% e 5,9% respectivamente) que no grupo controle. No fluido peritoneal também foi maior no grupo caso (Mh: 27,8%; Mg: 40,7%; Uu: 3,7% e HPV: 9,6%) do que o grupo controle. No tecido de biópsia, Mh (5,9%) e Mg (13,2%) foram maiores no grupo caso. M. genitalium no fluido peritoneal foi associado à maior produção de IFN-&#947; e IL-1&#946; (p < 0,05). O perfil de downregulation de genes da inflamação foi acentuado na presença de M. genitalium. Upregulation ocorreu na presença de M. hominis. Mollicutes podem influenciar na resposta imune na endometriose. / Endometriosis is a disease characterized by the presence of endometrium outside of uterus. This study aimed to detect Mollicutes (M. genitalium, M. hominis, U. urealyticum and U. parvum), HPV and N. gonorrhoeae in samples of endocervical swab, peritoneal fluid and biopsied tissue from women with (case group) and without endometriosis (control group) and evaluate the finds with endometriosis. In swab samples the prevalence of M. hominis (Mh), M. genitalium (Mg), U. urealyticum (Uu) and HPV were higher in case group (43.7%, 14.1%, 8.5% e 5.9% respectively) than the control group. In the peritoneal fluid it was higher in the case group as well (Mh: 27.8%; Mg: 40.7%; Uu: 3.7% e HPV: 9.6%).In the biopsied tissue, Mh (5.9%) and Mg (13.2%) were higher in the case group. M. genitalium in the peritoneal fluid was associated to a higher production of IFN-&#947; and IL-1&#946;. Downregulation of inflammatory genes were accentuated when M. genitalium was detected. Upregulation occurred when M. hominis was detected. Mollicutes could influence in the immune response on endometriosis.

A endometriose é uma doença caracterizada pela presença de endométrio fora do útero. O estudo objetivou detectar Mollicutes (M. genitalium, M. hominis, U. urealyticum e U. parvum), HPV e N. gonorrhoeae em amostras de swab endocervical, fluido peritoneal e tecido de biópsia de mulheres com (grupo caso) e sem endometriose (grupo controle) e avaliar os achados com a endometriose. No swab endocervical, prevalências de M. hominis (Mh), M. genitalium (Mg), U. urealyticum (Uu) e HPV foram maiores no grupo caso (43,7%, 14,1%, 8,5% e 5,9% respectivamente) que no grupo controle. No fluido peritoneal também foi maior no grupo caso (Mh: 27,8%; Mg: 40,7%; Uu: 3,7% e HPV: 9,6%) do que o grupo controle. No tecido de biópsia, Mh (5,9%) e Mg (13,2%) foram maiores no grupo caso. M. genitalium no fluido peritoneal foi associado à maior produção de IFN-&#947; e IL-1&#946; (p < 0,05). O perfil de downregulation de genes da inflamação foi acentuado na presença de M. genitalium. Upregulation ocorreu na presença de M. hominis. Mollicutes podem influenciar na resposta imune na endometriose. / Endometriosis is a disease characterized by the presence of endometrium outside of uterus. This study aimed to detect Mollicutes (M. genitalium, M. hominis, U. urealyticum and U. parvum), HPV and N. gonorrhoeae in samples of endocervical swab, peritoneal fluid and biopsied tissue from women with (case group) and without endometriosis (control group) and evaluate the finds with endometriosis. In swab samples the prevalence of M. hominis (Mh), M. genitalium (Mg), U. urealyticum (Uu) and HPV were higher in case group (43.7%, 14.1%, 8.5% e 5.9% respectively) than the control group. In the peritoneal fluid it was higher in the case group as well (Mh: 27.8%; Mg: 40.7%; Uu: 3.7% e HPV: 9.6%).In the biopsied tissue, Mh (5.9%) and Mg (13.2%) were higher in the case group. M. genitalium in the peritoneal fluid was associated to a higher production of IFN-&#947; and IL-1&#946;. Downregulation of inflammatory genes were accentuated when M. genitalium was detected. Upregulation occurred when M. hominis was detected. Mollicutes could influence in the immune response on endometriosis.